Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.

The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open C, outward-occluded C and inward-open C.

Identification of a depupylation regulator for an essential enzyme in .

In , proteins that are posttranslationally modified with a prokaryotic ubiquitin-like protein (Pup) can be degraded by bacterial proteasomes. A single Pup-ligase and depupylase shape the pupylome, but the mechanisms regulating their substrate specificity are incompletely understood. Here, we identified a depupylation regulator, a protein called CoaX, through its copurification with the depupylase Dop.

A Road Map to Hepatitis C Elimination: Yesterday, Today, and Tomorrow.

There are an estimated 3.5 million people with hepatitis C virus (HCV) infection in the United States, resulting in 15 000 HCV-related deaths in 2019 and approximately $7 billion annually in healthcare costs. Although the United States had experienced declining incidence, since 2010 hepatitis C infections have rebounded.

Biomarkers for Cognitive Control, Response Inhibition, Aggressivity, Impulsivity, and Violence.

Deficits in cognitive control contribute to behavioral impairments across neuropsychiatric disorders. Cognitive control is captured as a construct in the Research Domain Construct (RDoC) matrix and incorporate subdomains of goal selection, response selection, and performance monitoring. Relevant tasks for these subdomains include the "AX" version of the continuous performance task (goal selection) and the Go/NoGo and Stop-Signal reaction time tasks (response selection).

Auditory Biomarkers of Neuropsychiatric Disorders in Nonhuman Primates.

Animal models of neuropsychiatric disorders with appropriate biomarkers can greatly inform the neurobiological basis of disorder-related deficits of cognitive and/or sensory processes. Given the genetic, physiologic, and behavioral similarities between humans and nonhuman primates (NHPs), NHP studies are monumentally important for preclinical translational research. Capitalizing on the NHP's similarities with human systems provides one of the best opportunities to gain detailed insight into the mechanisms underlying disorder-related symptoms and to accumulate a foundation of information for the development of therapeutic interventions.

Quantitative and Morphology-Based Deep Convolutional Neural Network Approaches for Osteosarcoma Survival Prediction in the Neoadjuvant and Metastatic Settings.

Purpose: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting.

Experimental Design: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia).

Trajectories of human brain functional connectome maturation across the birth transition.

Understanding the sequence and timing of brain functional network development at the beginning of human life is critically important from both normative and clinical perspectives. Yet, we presently lack rigorous examination of the longitudinal emergence of human brain functional networks over the birth transition. Leveraging a large, longitudinal perinatal functional magnetic resonance imaging (fMRI) data set, this study models developmental trajectories of brain functional networks spanning 25 to 55 weeks of post-conceptual gestational age (GA).

Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium.

Objectives: To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.

Methods: In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi).

Inverse-Weighted Quantile Regression With Partially Interval-Censored Data.

This paper introduces a novel approach to estimating censored quantile regression using inverse probability of censoring weighted (IPCW) methodology, specifically tailored for data sets featuring partially interval-censored data. Such data sets, often encountered in HIV/AIDS and cancer biomedical research, may include doubly censored (DC) and partly interval-censored (PIC) endpoints. DC responses involve either left-censoring or right-censoring alongside some exact failure time observations, while PIC responses are subject to interval-censoring.

Prenatal chemical exposures and the methylome: current evidence and opportunities for environmental epigenetics.

Exposure to pollutants and chemicals during critical developmental periods in early life can impact health and disease risk across the life course. Research in environmental epigenetics has provided increasing evidence that prenatal exposures affect epigenetic markers, particularly DNA methylation. In this article, we discuss the role of DNA methylation in early life programming and review evidence linking the intrauterine environment to epigenetic modifications, with a focus on exposure to tobacco smoke, metals, and endocrine-disrupting chemicals.

Dysfunctional activation of the default mode network in response inhibition in schizophrenia.

The aim of this study was to characterize dysfunctional cerebral activation in patients with schizophrenia while they performed a response inhibition task. To achieve this, performance on the task and functional magnetic resonance imaging (fMRI) were compared between healthy control subjects (HC) and patients with schizophrenia (SZ). We focused on the default mode network (DMN), as there is strong evidence in the literature that lack of DMN suppression in schizophrenia is associated with cognitive impairment including poor response inhibition.

Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target.

Digestive-system cancers represent major threats to human health; however, the mechanisms underlying tumorigenesis and radiochemotherapy resistance have remained elusive. Therefore, an urgent need exists for identifying key drivers of digestive system tumorigenesis and novel targeted therapeutics. The checkpoint kinase 2 (Chk2) regulates cell-cycle progression, and Chk2 dysregulation or Chk2 mutations can lead to the development of various cancers, which makes Chk2 an important research topic.

Bad company? The pericardium microbiome in people investigated for tuberculous pericarditis in an HIV-prevalent setting.

Background: The site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome.

Methods: People with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement.

A Site-Wise Reliability Analysis of the ABCD Diffusion Fractional Anisotropy and Cortical Thickness: Impact of Scanner Platforms.

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols.

Staff perspectives of barriers and facilitators to implementation of the Consult for Addiction Treatment and Care in Hospitals (CATCH) program in New York City safety net hospitals.

Background: In response to the heavy burden of untreated substance use disorders (SUD) in hospital patients, many health systems are implementing addiction consult services staffed by interprofessional teams that diagnose SUD, make recommendations for SUD care in the hospital, and link patients to post-discharge treatment. In 2018, the New York City public hospital system began rolling out the Consult for Addiction Treatment and Care in Hospitals (CATCH) program in six hospitals. CATCH teams are comprised of an addiction-trained medical provider, social worker or addiction counselor, and peer counselor.

Diagnostic Techniques for Infantile Subglottic Hemangiomas: A Scoping Review.

Objective: Infantile subglottic hemangioma (SGH) poses a risk of airway compromise if untreated. Traditionally, operative endoscopy (OH) diagnoses SGH, but since the discovery of beta-blockers' efficacy in treating infantile hemangiomas (IHs) in 2008, and advances in endoscopic technology, nonoperative methods have emerged. This review identifies endoscopic practices for diagnosing and monitoring infantile SGH during the oral beta-blocker treatment era.